Abstract

To understand how brain states and behaviors are generated by neural circuits, it would be useful to be able to perturb precisely the activity of specific cell types and pathways in the nonhuman primate nervous system. We used lentivirus to target the light-activated cation channel channelrhodopsin-2 (ChR2) specifically to excitatory neurons of the macaque frontal cortex. Using a laser-coupled optical fiber in conjunction with a recording microelectrode, we showed that activation of excitatory neurons resulted in well-timed excitatory and suppressive influences on neocortical neural networks. ChR2 was safely expressed, and could mediate optical neuromodulation, in primate neocortex over many months. These findings highlight a methodology for investigating the causal role of specific cell types in nonhuman primate neural computation, cognition, and behavior, and open up the possibility of a new generation of ultraprecise neurological and psychiatric therapeutics via cell-type-specific optical neural control prosthetics.

Comparison of Neural Activity Levels within Excited and Suppressed Single Units, before, during, and after Light Exposure

(A) Firing rate change during the beginning of light period (i.e., firing rate during beginning of light minus baseline firing rate) versus baseline firing rate, for excited cells (n = 15 excited single units). (B) Firing rate change during the after light period versus during the beginning of light period, for excited single units. (C) Time elapsed until activity recovery to baseline level after light cessation, versus firing rate change during the beginning of light period, for excited single units. (D) Firing rate change during the steady state period, versus baseline firing rate, for suppressed cells (n=16 suppressed single units). (E) Firing rate change during the after light period versus during the steady state period, for suppressed single units. (F) Time elapsed until activity recovery to baseline level after light cessation, versus firing rate change during the steady state period, for suppressed single units.